Durum wheat represents one of the main food source for numerous countries of the Mediterranean area. It is mainly used for pasta production, but also in an array of other regional foods such as flat bread, cous cous, burghoul, etc. Breeding activities for quality in durum wheat have been mainly targeted towards the production of high-yielding cultivars with superior pasta-making characteristics. The role played by the gluten proteins in influencing processing characteristics of semolina, and in particular by the low-molecular weight glutenin subunits, has been elucidated. This has resulted in the development of breeding strategies for modifying protein composition in a predictable way and releasing durum wheat cultivars capable of satisfying processors and consumers requirements. More recently, the strong evidences between diet and health are leading to focus breeding activities on nutritional aspects and enhancement of wheat kernel components of health value. Among these, starch composition represents an important target due its role in influencing both technological and nutritional aspects of wheat end-products. In particular, high amylose starch can play an important role on human health preventing the onset of important diseases. In this paper, the manipulation of proteins and starch with the final goal to tailor novel durum wheat cultivars with improved technological and nutritional characteristics will be presented.